1. Field of the Invention
The present invention relates to vesicle stabilization, and more particularly to such stabilization by suspending micellular particles such as vesicles in a polymeric gel matrix.
2. Description of Prior Art
The use of micellular particles such as phospholipid vesicles (or liposomes as they are commonly referred to) as carriers for pharmaceutical and diagnostic agents has been the subject of extensive investigation, Ryman B.E., et al., Ann. N.Y. Acad. Sci., 308, 281 (1978); Gregoriadis, G., Ed., "Liposome Technology", CRC Press, Inc., Boca Raton, Fla., Vol. II (1984); Fendler J.H., Acc. Chem. Res., 13, 7 (1980); and Weinstein J.N., et al., Science, 204, 188 (1979). Examples of the potential application of phospholipid vesicles include consideration as carriers of enzymes, drugs (particularly anti-tumor drugs), chelating agents, hormones, radionuclides, cell-modifying substances, antigens, antibodies, interferon inducers, and virus subunit particles. However, liposomes (especially small sonicated vesicles) are thermodynamically unstable at temperatures below the phase transition temperature, and tend to aggregate or fuse, to form larger unilamellar vesicles on long-term storage, Sheetz M.P., et al., Biochemistry, 11, 4573 (1972); Lawaczeck R.L., et al., Biochem, Biophys. Acta, 443, 313 (1976); Larrabee H.L., Biochemistry, 18, 3321 (1978); and Shullery S.E., et al., Biochemistry, 19, 3919 (1980).
Aggregation or fusion of the small particles into larger particles alters the properties of the vesicles, which can in turn modify the permeability of the vesicles and in vivo biodistribution, Kao Y.J., et al., Biochem. Biophys. Acta., 677, 453 (1981); and Abra R.M., et al., Biochem. Biophys. Acta., 666, 493 (1981). It is accordingly highly important to be able to store micellular particles without having the particles aggregate or fuse together with the resultant potential change in important properties.